Cetirizine is a generic name for 2-[2-[4-[(4-chlorphenyl)phenylmethyl]-1-piperazinyl]ethoxy]-acetic acid and is typically provided as a dihydrochloride salt. Cetirizine is an orally active and selective H1-receptor antagonist currently prescribed for the treatment of seasonal allergies in patients aged 2 years and older. The current commercial products (Zyrtec™) are available as a white, film-coated, immediate release oral tablet in 5 and 10 mgA strengths and a sweet flavored syrup containing cetirizine hydrochloride at a concentration of 1 mg/ml for pediatric use. European patents Nos. 058,146; 294,993; and 357,369; and also WO 92/02212 describe cetirizine formulations for the controlled or continuous release of cetirizine in the form of tablets and capsules. Oral formulations in the form of a cough syrup are disclosed in WO 94/08551.
For patients, such as children, who have difficulty swallowing conventional tablets or capsules, chewable tablets are widely used in the pharmaceutical industry. In addition, chewable tablets avoid mishaps that may occur with liquids, such as spillage and stains.
One of the drawbacks to oral delivery systems however, is the situation where the drug to be administered is bitter, bad-tasting, odorous or in some manner unpleasant especially to children. Many efforts have been made in the past to “taste mask” these compounds either through elaborate flavor and/or sweetener delivery systems, adsorption of the drug within another material or by encapsulation with a polymer, fat, carbohydrate or other like material. These taste-masking methods basically prevent the bitter tasting components of the drug from contacting the taste-buds during oral ingestion yet break down and release the active upon dissolution in the stomach.
For example, U.S. Pat. No. 4,650,663 discloses the preparation of an oral pharmaceutical delivery system in which an unpleasant tasting anti-tussive such as noscapine, carbetapentane citrate or clophedianol hydrochloride is adsorbed onto magnesium silicate flakes and incorporated into a chewable tablet or lozenge. The adsorbate allegedly masks the bitter taste to an almost negligible level to encourage better patient compliance.
U.S. Pat. No. 6,027,746 discloses a soft chewable gelatin capsule having incorporated therein a drug dispersed in an oral suspension comprising a medicament adsorbate which masks bitter or bad-tasting pharmaceutical actives (such as antihistamines, decongestants and the like).
U.S. Pat. No. 6,270,790 discloses a soft, convex-shaped compressed chewable tablets. Active agents having a bitter or bad taste are masked by coating the drug with a 90:10 to 50:50 polymer blend of cellulose acetate or cellulose acetate butyrate and polyvinyl pyrrolidone or hydroxypropyl cellulose. However, coatings require an additional manufacturing step which adds to the manufacturing costs of the tablet.
U.S. Pat. No. 3,558,600 describes a method for masking the bitter taste of antihistamines belonging to the family of substituted 1-(p-chloro-benzhydryl)-piperazine. This method consists of transforming the active substance in the form of a free base into its long-chain alkyl sulfate salt, such as stearyl sulfate.
Another known method for masking the taste of active ingredients consists of forming an inclusion complex between the active ingredient and a cyclodextrin. In this case, the masking of the taste results from the trapping of the active ingredient, which cannot be released while it is in the mouth. The use of beta-cyclodextrin with cetirizine is described in WO 99/01133.
There still exists a need for a palatable formulation for cetirizine medicaments that assist in compliance especially with children.